TARGETED RESPONSIVE MR AND PET AGENTS FOR B-CELL IMAGING

用于 B 细胞成像的靶向响应 MR 和 PET 试剂

• 批准号: 7897697
• 负责人: Dean Sherry
• 金额: $ 31.44万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7897697
• 关键词: Acetates; Acetyl Coenzyme A; Animal Experiments; Animal Model; Animals; Arts; B-Lymphocytes; Binding; Biological; Blood Glucose; Calcium Channel; Carbon; Cell Line; Cell physiology; Cell surface; Cells; Citrate (si)-Synthase; Citric Acid Cycle; Collaborations; Complex; Detection; Development; Dose; Electron Transport; Environment; Enzymes; Exocytosis; Funding; Glucose; Glucose Transporter; Glucose-6-Phosphate; Glycolysis; Goals; Human; Image; Imidazole; Insulin; Islet Cell; Islets of Langerhans; Label; Ligands; Lipids; Magnetic Resonance Imaging; Measures; Metabolic; Metabolic Pathway; Metabolism; Mitochondria; Mole the mammal; Molecular Weight; NADH; Non-Insulin-Dependent Diabetes Mellitus; Organ; Oxaloacetates; Oxidation-Reduction; Oxidative Phosphorylation; Pan Genus; Pancreas; Peptide T; Peptides; Perfusion; Phage Display; Potassium Channel; Principal Investigator; Propionates; Protein Kinase; Proteins; Pyruvate; Pyruvates; RIPK2 gene; Rattus; Regulation; Relative (related person); Reporting; Resolution; Secretory Vesicles; Signal Transduction; Specificity; Surface; System; Techniques; Technology; Testing; Translating; Water; Work; base; carboxylation; cellular imaging; copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); cyclen; design; glucose metabolism; glucose sensor; imaging modality; in vivo; indexing; insulin secretion; insulinoma; islet; molecular imaging; novel; oxidation; programs; research clinical testing; research study; response; tool; uptake; voltage

The goal of Project 2 is to merge the metabolic strategies of Project 1 and islet targeting core (Core B) and with state-of-the-art imaging agent technologies to create novel PET and MR agents for molecular imaging of the b-cell in vivo. Our goal is to develop imaging agents that not only target the pancreatic b-cell in vivo but also respond to b-cell metabolism by functional activation. Before moving to animal experiments, we will initially develop a platform for both high resolution MR and PET imaging of cultured rat b-cells and isolated rat islets and use this technology to screen for entrapment of redox sensitive PET agents (64Cu-ATSM) and redox sensitive PARACEST agents (cyclen-based tetraamide complexes of Eu3+ or Tm3+) in b-cells. Proof of concept studies on agents that specifically target b-cells will be performed using multimeric peptides identified by phage display panning of insulinoma INS 832/1 cells and isolated rat islets. Given these peptides or others identified in Core B, we will develop an efficient labeling approach to attach either 18F or cyclen-based ligands to all targeting peptides to create MR (pH sensitive Gd3+-based agents, PARACESTbased Zn2+ and glucose sensors) and PET agents (both 18F and 64Cu) to measure a) b-cell mass and b) bcell function. A final aim is to combine the technologies of aims 1 & 2 to create targeted & responsive MR and PET agents that not only report b-cell mass but also provide an imaging index of b-cell function.

项目2的目标是合并项目1的代谢策略和目标核心（核心B）和 使用最先进的成像剂技术来创建新颖的宠物和MR代理，以分子成像 B细胞在体内。我们的目标是开发成像剂，不仅针对体内胰腺B细胞，还针对 还通过功能激活对B细胞代谢做出反应。在进行动物实验之前，我们将 最初开发一个用于培养的大鼠B细胞和孤立的高分辨率MR和PET成像的平台 大鼠胰岛，并使用此技术筛选氧化还原敏感宠物代理（64cu-atsm）和 B细胞中的氧化还原敏感的寄生虫（EU3+或TM3+的基于Cyclen的四酰胺复合物）。证明 对特定针对B细胞的药物的概念研究将使用多聚肽进行 通过噬菌体显示胰岛素瘤INS 832/1细胞和分离的大鼠胰岛的平移鉴定。鉴于这些 在核心B中鉴定出的肽或其他肽，我们将开发一种有效的标签方法，以附加18F或 基于Cyclen的所有靶向肽以创建MR的配体 Zn2+和葡萄糖传感器）和宠物剂（18F和64CU）测量A）B细胞质量和B）B） 功能。最终目的是结合目标1和2的技术，以创建有针对性和响应的MR 以及不仅报告B细胞质量而且还提供B细胞功能的成像索引的宠物代理。